title: Tissue factor pathway inhibitor-2: a novel gene involved in zebrafish central nervous system development.
abstract: Tissue factor pathway inhibitor-2 (Tfpi-2) is an important serine protease inhibitor in the extracellular matrix (ECM), but its precise physiological significance remains unknown. This work is part of a series of studies intended to investigate functional roles of Tfpi-2 and explore the underlying molecular mechanisms. First, we cloned and identified zebrafish Tfpi-2 (zTfpi-2) as an evolutionarily conserved protein essential for zebrafish development. We also demonstrated that ztfpi-2 is mainly expressed in the central nervous system (CNS) of zebrafish, and embryonic depletion of ztfpi-2 caused severe CNS defects. In addition, changes of neural markers, including pax2a, egr2b, huC, ngn1, gfap and olig2, confirmed the presence of developmental abnormalities in the relevant regions of ztfpi-2 morphants. Using microarray analysis, we found that members of the Notch pathway, especially her4 and mib, which mediate lateral inhibition in CNS development, were also downregulated. Intriguingly, both her4 and mib were able to partially rescue the ztfpi-2 morphant phenotype. Furthermore, Morpholino knockdown of ztfpi-2 resulted in upregulation of neuronal markers while downregulation of glial markers, providing evidence that the Notch pathway is probably involved in ztfpi-2-mediated CNS development.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Wenhao
authors.initials: W
authors.lastname: Zhou
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Deng
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
authors.forename: Zuohua
authors.initials: Z
authors.lastname: Mao
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002490:Central Nervous System / Q000196:embryology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D053491:Proteinase Inhibitory Proteins, Secretory / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D018076:DNA, Complementary; D006023:Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C000596118:tfpi2 protein, zebrafish; C021240:tissue-factor-pathway inhibitor 2; D049452:Green Fluorescent Proteins
keywords: CNS; Functions; Notch pathway; Tfpi-2; Zebrafish